Discovery of coding genetic variants influencing diabetes-related serum biomarkers and their impact on risk of type 2 diabetes

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Discovery of coding genetic variants influencing diabetes-related serum biomarkers and their impact on risk of type 2 diabetes. / Ahluwalia, Tarun Veer Singh; Allin, Kristine Højgaard; Sandholt, Camilla Helene; Sparsø, Thomas Hempel; Jørgensen, Marit Eika; Rowe, Michael; Christensen, Cramer; Brandslund, Ivan; Lauritzen, Torsten; Linneberg, Allan; Husemoen, Lise-Lotte; Jørgensen, Torben; Hansen, Torben; Grarup, Niels; Pedersen, Oluf.

In: The Journal of clinical endocrinology and metabolism, Vol. 100, No. 4, 04.2015, p. E664-71.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Ahluwalia, TVS, Allin, KH, Sandholt, CH, Sparsø, TH, Jørgensen, ME, Rowe, M, Christensen, C, Brandslund, I, Lauritzen, T, Linneberg, A, Husemoen, L-L, Jørgensen, T, Hansen, T, Grarup, N & Pedersen, O 2015, 'Discovery of coding genetic variants influencing diabetes-related serum biomarkers and their impact on risk of type 2 diabetes', The Journal of clinical endocrinology and metabolism, vol. 100, no. 4, pp. E664-71. https://doi.org/10.1210/jc.2014-3677

APA

Ahluwalia, T. V. S., Allin, K. H., Sandholt, C. H., Sparsø, T. H., Jørgensen, M. E., Rowe, M., ... Pedersen, O. (2015). Discovery of coding genetic variants influencing diabetes-related serum biomarkers and their impact on risk of type 2 diabetes. The Journal of clinical endocrinology and metabolism, 100(4), E664-71. https://doi.org/10.1210/jc.2014-3677

Vancouver

Ahluwalia TVS, Allin KH, Sandholt CH, Sparsø TH, Jørgensen ME, Rowe M et al. Discovery of coding genetic variants influencing diabetes-related serum biomarkers and their impact on risk of type 2 diabetes. The Journal of clinical endocrinology and metabolism. 2015 Apr;100(4):E664-71. https://doi.org/10.1210/jc.2014-3677

Author

Ahluwalia, Tarun Veer Singh ; Allin, Kristine Højgaard ; Sandholt, Camilla Helene ; Sparsø, Thomas Hempel ; Jørgensen, Marit Eika ; Rowe, Michael ; Christensen, Cramer ; Brandslund, Ivan ; Lauritzen, Torsten ; Linneberg, Allan ; Husemoen, Lise-Lotte ; Jørgensen, Torben ; Hansen, Torben ; Grarup, Niels ; Pedersen, Oluf. / Discovery of coding genetic variants influencing diabetes-related serum biomarkers and their impact on risk of type 2 diabetes. In: The Journal of clinical endocrinology and metabolism. 2015 ; Vol. 100, No. 4. pp. E664-71.

Bibtex

@article{9bd4e0c6b3a04b22a4ff46cd2e0cd762,
title = "Discovery of coding genetic variants influencing diabetes-related serum biomarkers and their impact on risk of type 2 diabetes",
abstract = "CONTEXT: Type 2 diabetes (T2D) prevalence is spiraling globally, and knowledge of its pathophysiological signatures is crucial for a better understanding and treatment of the disease.OBJECTIVE: We aimed to discover underlying coding genetic variants influencing fasting serum levels of nine biomarkers associated with T2D: adiponectin, C-reactive protein, ferritin, heat shock 70-kDa protein 1B, IGF binding protein 1 and IGF binding protein 2, IL-18, IL-2 receptor-α, and leptin.DESIGN AND PARTICIPANTS: A population-based sample of 6215 adult Danes was genotyped for 16 340 coding single-nucleotide polymorphisms and were tested for association with each biomarker. Identified loci were tested for association with T2D through a large-scale meta-analysis involving up to 17 024 T2D cases and up to 64 186 controls.RESULTS: We discovered 11 associations between single-nucleotide polymorphisms and five distinct biomarkers at a study-wide P < 3.4 × 10(-7). Nine associations were novel: IL18: BIRC6, RAD17, MARVELD2; ferritin: F5; IGF binding protein 1: SERPING1, KLKB, GCKR, CELSR2, and heat shock 70-kDa protein 1B: CFH. Three of the identified loci (CELSR2, HNF1A, and GCKR) were significantly associated with T2D, of which the association with the CELSR2 locus has not been shown previously.CONCLUSION: The identified loci influence processes related to insulin signaling, cell communication, immune function, apoptosis, DNA repair, and oxidative stress, all of which could provide a rationale for novel diabetes therapeutic strategies.",
author = "Ahluwalia, {Tarun Veer Singh} and Allin, {Kristine H{\o}jgaard} and Sandholt, {Camilla Helene} and Spars{\o}, {Thomas Hempel} and J{\o}rgensen, {Marit Eika} and Michael Rowe and Cramer Christensen and Ivan Brandslund and Torsten Lauritzen and Allan Linneberg and Lise-Lotte Husemoen and Torben J{\o}rgensen and Torben Hansen and Niels Grarup and Oluf Pedersen",
year = "2015",
month = "4",
doi = "10.1210/jc.2014-3677",
language = "English",
volume = "100",
pages = "E664--71",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Oxford University Press",
number = "4",

}

RIS

TY - JOUR

T1 - Discovery of coding genetic variants influencing diabetes-related serum biomarkers and their impact on risk of type 2 diabetes

AU - Ahluwalia, Tarun Veer Singh

AU - Allin, Kristine Højgaard

AU - Sandholt, Camilla Helene

AU - Sparsø, Thomas Hempel

AU - Jørgensen, Marit Eika

AU - Rowe, Michael

AU - Christensen, Cramer

AU - Brandslund, Ivan

AU - Lauritzen, Torsten

AU - Linneberg, Allan

AU - Husemoen, Lise-Lotte

AU - Jørgensen, Torben

AU - Hansen, Torben

AU - Grarup, Niels

AU - Pedersen, Oluf

PY - 2015/4

Y1 - 2015/4

N2 - CONTEXT: Type 2 diabetes (T2D) prevalence is spiraling globally, and knowledge of its pathophysiological signatures is crucial for a better understanding and treatment of the disease.OBJECTIVE: We aimed to discover underlying coding genetic variants influencing fasting serum levels of nine biomarkers associated with T2D: adiponectin, C-reactive protein, ferritin, heat shock 70-kDa protein 1B, IGF binding protein 1 and IGF binding protein 2, IL-18, IL-2 receptor-α, and leptin.DESIGN AND PARTICIPANTS: A population-based sample of 6215 adult Danes was genotyped for 16 340 coding single-nucleotide polymorphisms and were tested for association with each biomarker. Identified loci were tested for association with T2D through a large-scale meta-analysis involving up to 17 024 T2D cases and up to 64 186 controls.RESULTS: We discovered 11 associations between single-nucleotide polymorphisms and five distinct biomarkers at a study-wide P < 3.4 × 10(-7). Nine associations were novel: IL18: BIRC6, RAD17, MARVELD2; ferritin: F5; IGF binding protein 1: SERPING1, KLKB, GCKR, CELSR2, and heat shock 70-kDa protein 1B: CFH. Three of the identified loci (CELSR2, HNF1A, and GCKR) were significantly associated with T2D, of which the association with the CELSR2 locus has not been shown previously.CONCLUSION: The identified loci influence processes related to insulin signaling, cell communication, immune function, apoptosis, DNA repair, and oxidative stress, all of which could provide a rationale for novel diabetes therapeutic strategies.

AB - CONTEXT: Type 2 diabetes (T2D) prevalence is spiraling globally, and knowledge of its pathophysiological signatures is crucial for a better understanding and treatment of the disease.OBJECTIVE: We aimed to discover underlying coding genetic variants influencing fasting serum levels of nine biomarkers associated with T2D: adiponectin, C-reactive protein, ferritin, heat shock 70-kDa protein 1B, IGF binding protein 1 and IGF binding protein 2, IL-18, IL-2 receptor-α, and leptin.DESIGN AND PARTICIPANTS: A population-based sample of 6215 adult Danes was genotyped for 16 340 coding single-nucleotide polymorphisms and were tested for association with each biomarker. Identified loci were tested for association with T2D through a large-scale meta-analysis involving up to 17 024 T2D cases and up to 64 186 controls.RESULTS: We discovered 11 associations between single-nucleotide polymorphisms and five distinct biomarkers at a study-wide P < 3.4 × 10(-7). Nine associations were novel: IL18: BIRC6, RAD17, MARVELD2; ferritin: F5; IGF binding protein 1: SERPING1, KLKB, GCKR, CELSR2, and heat shock 70-kDa protein 1B: CFH. Three of the identified loci (CELSR2, HNF1A, and GCKR) were significantly associated with T2D, of which the association with the CELSR2 locus has not been shown previously.CONCLUSION: The identified loci influence processes related to insulin signaling, cell communication, immune function, apoptosis, DNA repair, and oxidative stress, all of which could provide a rationale for novel diabetes therapeutic strategies.

U2 - 10.1210/jc.2014-3677

DO - 10.1210/jc.2014-3677

M3 - Journal article

VL - 100

SP - E664-71

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 4

ER -

ID: 135494309